TW548277B - Orally active androgens - Google Patents

Orally active androgens Download PDF

Info

Publication number: TW548277B
Authority: TW; Taiwan
Prior art keywords: product; patent application; ethyl; solution; alkyl
Prior art date: 1999-07-16

Application number

TW089112646A

Other languages

English (en)

Chinese (zh)

Inventor

Hubert Jan Jozef Loozen

Dirk Leysen

Der Louw Jaap Van

Original Assignee

Akzo Nobel Nv

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-07-16

Filing date

2000-06-27

Publication date

2003-08-21

2000-06-27 Application filed by Akzo Nobel Nv filed Critical Akzo Nobel Nv

2003-08-21 Application granted granted Critical

2003-08-21 Publication of TW548277B publication Critical patent/TW548277B/zh

Links

239000003098 androgen Substances 0.000 title abstract description 10
229940030486 androgens Drugs 0.000 title abstract description 4
150000001875 compounds Chemical class 0.000 claims abstract description 36
125000000217 alkyl group Chemical group 0.000 claims abstract description 22
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
239000001257 hydrogen Substances 0.000 claims abstract description 10
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 10
125000000304 alkynyl group Chemical group 0.000 claims abstract description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 3
-1 steroid compounds Chemical class 0.000 claims description 36
238000011049 filling Methods 0.000 claims description 29
230000002079 cooperative effect Effects 0.000 claims description 17
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
229920002554 vinyl polymer Polymers 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
239000003795 chemical substances by application Substances 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 4
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
125000006017 1-propenyl group Chemical group 0.000 claims description 3
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims description 3
229910052757 nitrogen Inorganic materials 0.000 claims description 3
239000007789 gas Substances 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims 4
206010002261 Androgen deficiency Diseases 0.000 claims 2
239000003937 drug carrier Substances 0.000 claims 1
238000002360 preparation method Methods 0.000 claims 1
229910052736 halogen Inorganic materials 0.000 abstract description 7
150000002367 halogens Chemical group 0.000 abstract description 7
150000002431 hydrogen Chemical group 0.000 abstract description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 abstract description 3
125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 abstract description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 2
125000002252 acyl group Chemical group 0.000 abstract 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
239000000047 product Substances 0.000 description 109
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
239000000243 solution Substances 0.000 description 72
238000000034 method Methods 0.000 description 43
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
239000012074 organic phase Substances 0.000 description 34
229920006395 saturated elastomer Polymers 0.000 description 34
239000012267 brine Substances 0.000 description 33
239000000203 mixture Substances 0.000 description 33
239000011541 reaction mixture Substances 0.000 description 33
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 31
229910052938 sodium sulfate Inorganic materials 0.000 description 30
235000011152 sodium sulphate Nutrition 0.000 description 30
238000003756 stirring Methods 0.000 description 29
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 26
150000003431 steroids Chemical class 0.000 description 22
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
238000000746 purification Methods 0.000 description 20
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
238000006243 chemical reaction Methods 0.000 description 18
229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
235000017557 sodium bicarbonate Nutrition 0.000 description 18
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
239000007864 aqueous solution Substances 0.000 description 13
238000004587 chromatography analysis Methods 0.000 description 13
235000019270 ammonium chloride Nutrition 0.000 description 12
125000004432 carbon atom Chemical group C* 0.000 description 12
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 12
238000010992 reflux Methods 0.000 description 12
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
229940088597 hormone Drugs 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
238000001816 cooling Methods 0.000 description 8
230000000694 effects Effects 0.000 description 8
239000005556 hormone Substances 0.000 description 8
150000002576 ketones Chemical class 0.000 description 8
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
150000003839 salts Chemical class 0.000 description 8
238000007259 addition reaction Methods 0.000 description 7
239000008280 blood Substances 0.000 description 7
210000004369 blood Anatomy 0.000 description 7
238000004440 column chromatography Methods 0.000 description 7
229910052744 lithium Inorganic materials 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 6
210000004907 gland Anatomy 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
229910021529 ammonia Inorganic materials 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 description 4
230000000875 corresponding effect Effects 0.000 description 4
125000000468 ketone group Chemical group 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
229910021590 Copper(II) bromide Inorganic materials 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 3
239000012043 crude product Substances 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 3
238000011534 incubation Methods 0.000 description 3
238000006317 isomerization reaction Methods 0.000 description 3
239000007788 liquid Substances 0.000 description 3
210000005229 liver cell Anatomy 0.000 description 3
238000005259 measurement Methods 0.000 description 3
230000002503 metabolic effect Effects 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
229940127234 oral contraceptive Drugs 0.000 description 3
239000003539 oral contraceptive agent Substances 0.000 description 3
238000012856 packing Methods 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
239000002243 precursor Substances 0.000 description 3
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
235000019345 sodium thiosulphate Nutrition 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
238000012360 testing method Methods 0.000 description 3
PRXNKYBFWAWBNZ-UHFFFAOYSA-N trimethylphenylammonium tribromide Chemical compound Br[Br-]Br.C[N+](C)(C)C1=CC=CC=C1 PRXNKYBFWAWBNZ-UHFFFAOYSA-N 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
ULAADVBNYHGIBP-GFEQUFNTSA-N (8r,9s,13s,14s,17s)-3-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-ol Chemical compound C1C[C@]2(C)[C@@H](O)CC[C@H]2[C@@H]2CCC3=CC(OC)=CC=C3[C@H]21 ULAADVBNYHGIBP-GFEQUFNTSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 description 2
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 2
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
239000005977 Ethylene Substances 0.000 description 2
HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
150000001241 acetals Chemical class 0.000 description 2
239000002253 acid Substances 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
238000003556 assay Methods 0.000 description 2
238000005893 bromination reaction Methods 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
238000001311 chemical methods and process Methods 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
229910052802 copper Inorganic materials 0.000 description 2
239000010949 copper Substances 0.000 description 2
GEZOTWYUIKXWOA-UHFFFAOYSA-L copper;carbonate Chemical compound [Cu+2].[O-]C([O-])=O GEZOTWYUIKXWOA-UHFFFAOYSA-L 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
238000001514 detection method Methods 0.000 description 2
229940011871 estrogen Drugs 0.000 description 2
239000000262 estrogen Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
210000003494 hepatocyte Anatomy 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
150000002471 indium Chemical class 0.000 description 2
239000011630 iodine Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
229910052808 lithium carbonate Inorganic materials 0.000 description 2
238000011068 loading method Methods 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
239000012071 phase Substances 0.000 description 2
229960005235 piperonyl butoxide Drugs 0.000 description 2
239000011591 potassium Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
235000010265 sodium sulphite Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
- C07J1/0074—Esters
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Endocrinology (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Diabetes (AREA)
Reproductive Health (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

TW089112646A 1999-07-16 2000-06-27 Orally active androgens TW548277B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP99202348		1999-07-16

Publications (1)

Publication Number	Publication Date
TW548277B true TW548277B (en)	2003-08-21

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TW089112646A TW548277B (en)	1999-07-16	2000-06-27	Orally active androgens

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US (3)	US6313108B1 (cs)
EP (1)	EP1203011B1 (cs)
JP (1)	JP2003505394A (cs)
KR (1)	KR20020092890A (cs)
CN (1)	CN1360589A (cs)
AR (1)	AR024746A1 (cs)
AT (1)	ATE257159T1 (cs)
AU (1)	AU770412B2 (cs)
BR (1)	BR0012489A (cs)
CA (1)	CA2379223A1 (cs)
CO (1)	CO5200765A1 (cs)
CZ (1)	CZ2002192A3 (cs)
DE (1)	DE60007530T2 (cs)
ES (1)	ES2213596T3 (cs)
HK (1)	HK1043797A1 (cs)
HU (1)	HUP0201952A3 (cs)
IL (1)	IL147332A0 (cs)
MX (1)	MXPA02000601A (cs)
NO (1)	NO20020222L (cs)
NZ (1)	NZ516525A (cs)
PE (1)	PE20010330A1 (cs)
PL (1)	PL353007A1 (cs)
RU (1)	RU2002103883A (cs)
SK (1)	SK712002A3 (cs)
TR (1)	TR200200076T2 (cs)
TW (1)	TW548277B (cs)
WO (1)	WO2001005806A1 (cs)
ZA (1)	ZA200200106B (cs)

Families Citing this family (24)

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Publication number	Priority date	Publication date	Assignee	Title
EP1212345B1 (en) *	1999-04-06	2003-08-06	Akzo Nobel N.V.	Orally active 7-alpha-alkyl androgens
EP1272196B1 (en) *	2000-03-31	2006-08-02	THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES	Methods of making the 4-n-butylcyclohexanoic and the undecanoic acid esters of (7 alpha,11 beta)-dimethyl-17 beta-hydroxy-4-estren-3-one and their medical use
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Also Published As

Publication number	Publication date
WO2001005806A1 (en)	2001-01-25
ZA200200106B (en)	2003-06-25
US6780854B2 (en)	2004-08-24
US6313108B1 (en)	2001-11-06
MXPA02000601A (es)	2002-07-30
US6541465B2 (en)	2003-04-01
DE60007530D1 (de)	2004-02-05
JP2003505394A (ja)	2003-02-12
NZ516525A (en)	2003-06-30
US20030087886A1 (en)	2003-05-08
IL147332A0 (en)	2002-08-14
CO5200765A1 (es)	2002-09-27
NO20020222L (no)	2002-01-25
HUP0201952A3 (en)	2003-10-28
EP1203011B1 (en)	2004-01-02
CZ2002192A3 (cs)	2002-06-12
RU2002103883A (ru)	2004-02-27
TR200200076T2 (tr)	2002-04-22
PE20010330A1 (es)	2001-03-22
SK712002A3 (en)	2002-06-04
CN1360589A (zh)	2002-07-24
DE60007530T2 (de)	2004-12-23
PL353007A1 (en)	2003-09-22
AR024746A1 (es)	2002-10-23
BR0012489A (pt)	2002-04-02
KR20020092890A (ko)	2002-12-12
ATE257159T1 (de)	2004-01-15
NO20020222D0 (no)	2002-01-15
CA2379223A1 (en)	2001-01-25
AU6562900A (en)	2001-02-05
AU770412B2 (en)	2004-02-19
HUP0201952A2 (en)	2002-10-28
ES2213596T3 (es)	2004-09-01
EP1203011A1 (en)	2002-05-08
HK1043797A1 (zh)	2002-09-27
US20020022609A1 (en)	2002-02-21

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2006-06-21	MM4A	Annulment or lapse of patent due to non-payment of fees

Publication	Publication Date	Title
TW548277B (en)	2003-08-21	Orally active androgens
US10844088B2 (en)	2020-11-24	Process for the preparation of estetrol
KR100511815B1 (ko)	2005-09-05	플루오르화된 17α-알킬 사슬이 있는 항제스타겐성 스테로이드
JPS6069096A (ja)	1985-04-19	新規ステロイド
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TWI275593B (en)	2007-03-11	Novel androgens
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US6790843B1 (en)	2004-09-14	C-19-halogen-substituted steroids of the androst-9(11)-ene-series, methods for the production and use thereof
JP4279552B2 (ja)	2009-06-17	新規アンドロゲンとしてのメチレンステロイド
CN1481388A (zh)	2004-03-10	具有雄激素-孕激素混合活性的14(15)-不饱和的15-和/或16-取代的雄激素类
IE73240B1 (en)	1997-05-21	Steroids and therapeutic compositions containing same
MXPA06012849A (es)	2007-01-26	D-homo-17-cloro-16(17)eno esteroides.